BAM files

These are the bam files (raw data) from tumor molecular and genetic testing of two patients with non small cell lung cancer, mother and son. </p

Analysis of the role of RAS Family Mutations in Metastatic Colorectal Cancer (mCRC): Current Treatment Practice

A major challenge in metastatic colorectal cancer (mCRC) is the identification of specific biomarkers that are likely to predict which patients will benefit from a specific treatment. To this date, a number of studies have shown that a tumour's mutational profile influences treatment outcome in patients with mCRC and should, therefore, be used to guide treatment decision. For more than 5 years now, we know that patients with tumours harbouring mutations in exon 2, codons 12 and 13 of the KRAS oncogene gain no benefit from the administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (moAbs), Cetuximab and Panitumumab. It has just recently being elucidated that KRAS mutations outside codons 12 and 13 and mutations in the NRAS gene confer resistance to Cetuximab and Panitumumab, as well. Thus, since June 2013, the analysis of exons 2, 3 and 4 of KRAS and NRAS has been incorporated in daily clinical practice to improve patients’ selection for anti-EGFR moAbs treatment. Nevertheless, even if patients’ outcome under anti-EGFR moAbs therapy is improved with better selection based on Ras mutational status, more research is needed in this field; the matter is far from being resolved, since there are still a minority of wt RAS patients who do not respond upfront to such a treatment

Analysis of KRAS and NRAS mutations in Greek patients with metastatic Colorectal Cancer (mCRC) on the registry of the Gastro-intestinal Cancer Study Group (GIC-SG)

Several studies show that mutational profiles could influence treatment decisions in patients with metastatic CRC (mCRC). KRAS mutational status was the first step in biomarkers development in the era of molecular targeted therapies. Recently, NRAS mutational status was identified as an independent prognostic factor for the response to treatment with anti-EGFR moAbs. The aim of this observational study was to assess the feasibility of the KRAS/NRAS mutational analysis in patients with metastatic colorectal cancer in Greece and to identify any correlations with known clinical characteristics and histopathologic features

PKM2 Expression as Biomarker for Resistance to Oxaliplatin-Based Chemotherapy in Colorectal Cancer

The purpose of the current study is to investigate the prognostic significance of M2 isoform of pyruvate kinase (PKM2) mRNA expression loss in patients with operable colon cancer (CC). Two hundred sixty-two specimens from patients with stage-III or high-risk stage-II CC (group-A) treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy (FOLFOX), 118 specimens from metastatic CC patients (group-B) treated with FOLFOX, and 104 metastatic CC patients (group-C) treated with irinotecan-based chemotherapy were analyzed for PKM2, TS, ERCC1, MYC, and NEDD9 mRNA expression, as well as KRAS exon2 and BRAFV600E mutations. High PKM2 mRNA expression was correlated with left-sided located primaries (p = 0.001, group-A; p = 0.003, group-B; p = 0.001, group-C), high-grade tumors (p = 0.001, group-A; p = 0.017, group-B; p = 0.021, group-C), microsatellite-stable tumors (p &lt; 0.001, group-A), pericolic lymph nodes involvement (p = 0.018, group-A), and cMYC mRNA expression (p = 0.002, group-A; p = 0.008, group-B; p = 0.006, group-C). High PKM2 mRNA expression was correlated with significantly lower disease free survival (DFS) (p = 0.002) and overall survival (OS) (p = 0.001) in the group-A. Similarly, PKM2 mRNA expression was associated with significantly decreased progression free survival (PFS) (p = 0.001) and OS (p = 0.001) in group-B. On the contrary, no significant association for the PKM2 mRNA expression has been observed with either PFS (p = 0.612) or OS (p = 0.517) in group-C. To conclude, the current study provides evidence for the prediction of PKM2 mRNA expression oxaliplatin-based treatment resistance

A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy.

PurposeAn inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker's correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with metastatic colorectal cancer.Experimental designLCS6-variant and KRAS/BRAF mutational status was determined in 512 patients with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-variant allele to therapy exposure.ResultsIn this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-variant (TG/GG), which was found twice as frequently in the BRAF-mutated versus the wild-type (WT) group (P=0.03). LCS6-variant patients had significantly longer progression-free survival (PFS) with anti-EGFR mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P=0.019) and in the double WT (KRAS and BRAF) patient population (18 vs. 10.4 weeks; P=0.039). Combination therapy (mAbs plus chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy.ConclusionsLCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm the importance of this mutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation

A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy

PURPOSE: An inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker's correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with metastatic colorectal cancer. EXPERIMENTAL DESIGN: LCS6-variant and KRAS/BRAF mutational status was determined in 512 patients with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-variant allele to therapy exposure. RESULTS: In this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-variant (TG/GG), which was found twice as frequently in the BRAF-mutated versus the wild-type (WT) group (P=0.03). LCS6-variant patients had significantly longer progression-free survival (PFS) with anti-EGFR mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P=0.019) and in the double WT (KRAS and BRAF) patient population (18 vs. 10.4 weeks; P=0.039). Combination therapy (mAbs plus chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy. CONCLUSIONS: LCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm the importance of this mutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation